Diabetes and its complications impose significant economic consequences on individuals, families, health systems and countries. The annual expenditure for diabetes in 2007 in the USA alone was estimated to be over $170 billion, attributed to both direct and indirect costs (American Diabetes Association. Economic costs of diabetes in the U.S. in 2007. Diabetes Care. 2008 March, 31(3): 1-20). In 2010, Healthcare expenditures on diabetes are expected to account for 11.6% of the total worldwide healthcare expenditure. It is estimated that approximately 285 million people around the globe will have diabetes in 2010, representing 6.6% of the world's adult population, with a prediction for 438 million by 2030 (International Diabetes Federation. Diabetes Atlas, Fourth edition. International Diabetes Federation, 2009).
In the recent years, research has conclusively shown that improved glucose control reduces the long-term complications of diabetes (DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. North England Journal of Medicine. 1993 Sep. 30; 329(14): 977-986; UKPDS Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in subjects with type 2 diabetes (UKPDS33). The Lancet. 1998 Sep. 12; 352(9131): 837-853). According to the American Diabetes Association (ADA), self-monitoring of blood glucose (SMBG) has a positive impact on the outcome of therapy with insulin, oral agents and medical nutrition (American Diabetes Association. Clinical Practice Recommendations, Standards of medical care in diabetes. Diabetes Care. 2006 Jan 29: S4-S42). In its publication “Consensus Statement: A European Perspective”, the Diabetes Research Institute in Munich recommends SMBG for all types of diabetes treatment approaches, in order to achieve proper glucose control and values which are close to normal, without increasing the risk of hypoglycemia (Schnell O et al., Diabetes, Stoffwechsel and Herz, 2009; 4:285-289). Furthermore, special guidelines with proper recommendations were issued recently by the International Diabetes Federation (IDF), to support SMBG for non-insulin treated T2DM patients (Recommendations based on a workshop of the International Diabetes Federation Clinical Guidelines Taskforce in collaboration with the SMBG International Working group. Guidelines on Self-Monitoring of Blood Glucose in Non-Insulin Treated Type 2 Diabetics. International Diabetes Federation, 2009).
SMBG presents several benefits in both diabetes education and treatment. It can help facilitate individuals' diabetes management by providing an instrument for objective feedback on the impact of daily lifestyle habits, individual glucose profiles, including exercise and food intake impact on that profile, and thereby empower the individual to make necessary changes. Moreover, SMBG can support the healthcare team in providing individually tailored advice about life style components and blood glucose (BG) lowering medications, thus helping to achieve specific glycemic goals.
The inconvenience, expenses, pain and complexity involved in conventional (invasive) SMBG, however, lead to its underutilization, mainly in people with type 2 diabetes (Mollema E D, Snoek F J, Heine R J, Van der Ploeg H M. Phobia of self-injecting and self-testing in insulin treated diabetes patients: Opportunities for screening. Diabet Med. 2001; 18:671-674; Davidson M B, Castellanos M, Kain D, Duran P. The effect of self monitoring of blood glucose concentrations on glycated hemoglobin levels in diabetic patients not taking insulin: a blinded, randomized trial. Am J Med. 2005; 118(4):422-425; Hall R F, Joseph D H, Schwartz-Barcott D: Overcoming obstacles to behavior change in diabetes self-management. Diabetes Educ. 2003; 29:303-311). Availability of an accurate, painless, inexpensive and easy to operate device will encourage more frequent testing (Wagner J, Malchoff C, Abbott G. Invasiveness as a Barrier to Self-Monitoring of Blood Glucose in Diabetes. Diabetes Technology & Therapeutics. 2005 August; 7(4): 612-619; Soumerai S B, Mab C, Zhan F, Adams A, Baron M, Fajtova V, Ross-Degnan D. Effects of health maintenance organization coverage of self-monitoring devices on diabetes self-care and glycemic control. Arch Intern Med. 2004; 164:645-652), leading to tighter glucose control and delay/decrease of long-term complications and their associated healthcare costs.
Non-invasive (NI) glucose monitoring can decrease the cost of SMBG and increase meaningfully the frequency of testing. The main concern in NI methods is to achieve high accuracy results, despite the fact that no direct blood or interstitial fluid measurement is performed.
Therefore, as is well known in the medical arts, one of the more important blood components to measure for diagnostic purposes is glucose, especially for diabetic patients. The well-known and typical technique for determining blood glucose concentration is to secure a blood sample and apply that blood to an enzymatically medicated colorimetric strip or an electrochemical probe. Generally, this is accomplished from a finger prick. For diabetic patients who may need to measure blood glucose a few times a day, it can immediately be appreciated that this procedure causes a great deal of discomfort, considerable irritation to the skin and, particularly, the finger being pricked, and, of course, infection.
For many years, there have been a number of procedures for monitoring and measuring the glucose level in humans and animals. These methods, however, generally involve invasive techniques and, thus, have some degree of risk, or at least some discomfort, to the patient. Recently, some non-invasive procedures have been developed, but still they do not always provide optimum measurements of the blood glucose. At present, there has been no practical confirmed solution.
Most non-invasive monitoring techniques have focused on using incident radiation, which is capable of penetrating tissue and probing the blood. Currently known approaches to non-invasive glucose measurement are mainly based on optical technology. The less successful and relatively uncommon electrical measurements focus upon the dielectric properties of water solutions in a given frequency range, typically between 1-50 MHz. In one form or another, such methods attempt to monitor the influence of glucose or other analyzed concentration upon the dielectric frequency response of either the glucose itself or the secondary effect on the water.
Although investigations have been made into the use of acoustic monitoring, past studies have been primarily directed to the differences in acoustic velocity between organs. These studies have attempted to correlate acoustic velocity changes with chronic or continuous disease states. In addition, there is a large body of medical and scientific literature pertaining to the use of acoustic absorptive and scattering properties of organs for imaging, therapeutic and even diagnostic objectives.
In the prior art techniques, only one parameter is measured. Thus, the possibility of an error is increased.
Freger (U.S. Pat. No. 6,954,662) discloses a non-invasive technique and methods (but not devices) for measurements of the speed of sound through the blood, the conductivity of the blood, and the heat capacity of the blood. Thereafter, the glucose level for each of the three measurements is calculated and the final glucose value is determined by a weighted average of the three calculated glucose values.
While Freger mentions that measurements may be taken of the speed of sound through the blood, the conductivity of the blood, and the heat capacity of the blood, there is no disclosure of how any device can be constructed for effecting such measurements. The herein disclosed and claimed invention, therefore, is an improvement of Freger and specifies a specific device in which these measurements can be effected.
Therefore, there is a need for a more accurate non-invasive device for measuring glucose level, by means of monitoring multiple parameters in a single unitary device. It is, therefore, an object of the present invention to provide a device for non-invasively measuring glucose level in a subject. These objects are achieved by the features of the claims and the following description, in particular by the following preferred aspects of the invention relating to preferred additional and/or alternative embodiments.